Flexible Substituents Research Articles

Substituent groups effects on AIEgens of fluorenone derivatives: Optical properties, bioimaging, and LED devices

Understanding structure-property relationships is crucial for developing materials with a high fluorescence quantum yield (ΦF) and optimizing their performance. In this study, three fluorenone-carbazole-based molecules (FO-Cz1, FO-Cz2, and FO-Cz3) were synthesized, which have similar structures but varying substituent groups (carbazole, 3,6-di‑tert‑butyl‑9H-carbazole, and 3,6-diphenyl-9H-carbazole). The different substituent groups significantly changed the optical properties of the luminogens. The experimental results confirmed that FO-Cz1, FO-Cz2, and FO-Cz3 were AIEgens, and the introduction of a phenyl group gave FO-Cz3 strong αAIE(I/I0) and greater solid fluorescence quantum yields than FO-Cz1 and FO-Cz2. Analysis of photophysical properties, theoretical calculations, and X-ray crystallography revealed that the emission properties of FO-Cz1, FO-Cz2, and FO-Cz3 were influenced by the use of flexible substituent groups. The substituent groups avoided π-π stacking, reduced non-radiative transitions, and enhanced fluorescence in the aggregated state. Substituent groups on the benzene ring gave FO-Cz3 a tightly-packed structure and strong emission. It was used for cancer cell imaging and LED devices, in which FO-Cz3 exhibited high photostability and biocompatibility, making it a superior photosensitizer for bioimaging and applications in OLED devices. This research sheds light on the AIE behaviors of fluorenone complexes and offers valuable insights for the development of organic luminescent materials.

Cocatalytic Activity of the Furfuryl and Oxanorbornane-Substituted Guanidines in the Aldol Reaction Catalyzed by (S)-Proline

This work investigated the cocatalytic activity of recently prepared guanidinium salts containing an oxanorbornane subunit in an (S)-proline-catalyzed aldol reaction. The activity was interpreted by the diastereoselectivity of the reaction (anti/syn ratio) and for the most interesting polycyclic guanidinium salt, the enantioselectivity of the reaction was determined. The results indicated a negative impact on the oxanorbornane unit if present as the flexible substituent. For most of the tested aldehydes, the best cocatalysts provided enantioselectivities above 90% and above 95% at room temperature and 0 °C, respectively, culminating in >99.5% for 4–chloro– and 2–nitrobenzaldehyde as the substrate. The barriers for forming four possible enantiomers were calculated and the results for two anti–enantiomers are qualitatively consistent with the experiment. Obtained results suggest that the representatives of furfurylguanidinium and rigid polycyclic oxanorbornane-substituted guanidinium salts are good lead structures for developing new cocatalysts by tuning the chemical space around the guanidine moiety.

Potassium phenoxides bearing bulky yet flexible substituents as highly active catalysts for ring opening polymerization of biobased macrolactone of ethylene brassylate

Well-controlled and efficient ring opening polymerization of biobased ethylene brassylate is of great challenge due to its stainless ring structure that often results in inferior reactivities as well as the presence of two ester groups in the monomer that often lead to extensive intra-/inter- molecular transesterification side reactions. This report discloses a family of potassium phenoxide complexes that bear bulky yet flexible substituents. The bulky nature of the ligand could suppress undesired transesterification reactions, allowing the polymerization proceed in a well controlled manner, as revealed from the detailed kinetic studies that linear relationships between −ln(1-x) (x denotes the polymer yield) and the polymerization time and between molecular weights of the obtained polymers and polymer yields. The flexible substituents on the ligand allowed more monomer accessing to the active species, which eventually gave rise to TOFs in a range of 3604–3780 h−1, that were much higher than analogues in previous reports. Moreover, systematic evaluation of the polymerization behaviors demonstrated that the catalytic efficiency of the complexes was closely related to the steric nature of the metal center, increased the steric congestion would give rise to much lower monomer conversions. A plausible mechanism was proposed based on the polymerization results, and such a mechanism was further confirmed by NMR monitoring studies.

Design of an Azopolymer for Photo-Switchable Adhesive Applications

Significant research endeavors have been devoted to developing adhesives with reversible switching capabilities, allowing them to activate adhesion in response to diverse environmental stimuli. Among these, photo-switchable adhesives stand out as particularly promising. The presence of a photo-reversible solid-to-liquid transition, characterized by a transition temperature (TSL), in certain azobenzene-containing polymers offers a compelling avenue for creating such adhesives. The development of a method based on Atomic Force Microscopy to measure both the glass transition temperature (Tg) and TSL provided an opportunity to investigate the impact of various structural parameters on the solid-to-liquid transition of azopolymers. Our findings revealed that increasing the molecular weight (Mn) from 3400 to 8100 g/mol needed to achieve a highly cohesive adhesive resulted in an elevation in TSL (>10 °C), making the solid-to-liquid transition at room temperature more challenging. However, incorporating a highly flexible substituent at the para position of the azobenzene group proved effective in significantly reducing the TSL value (from 42 °C to 0 °C). This approach allows for the creation of photo-switchable adhesives with intriguing properties. We believe that our results establish a pathway toward developing a robust room-temperature photo-switchable adhesive.

Exploring a prototype for cooperative structural phase transition in cobalt(II) spin crossover compounds.

The creation of magnetically switchable materials that concurrently incorporate spin crossover (SCO) and a structural phase transition (SPT) presents a significant challenge in materials science. In this study, we prepared four structurally related cobalt(II)-based SCO compounds: two one-dimensional (1D) chains of {[(enbzp)Co(μ-L)](ClO4)2·sol}n (L = bpee, sol = 2MeOH·H2O, 1; L = bpea, sol = none, 2; enbzp = N,N'-(ethane-1,2-diyl)bis(1-phenyl-1-(pyridin-2-yl)methanimine); bpee = 1,2-bis(4-pyridyl)ethylene; and bpea = 1,2-bis(4-pyridyl)ethane) and their discrete segments, [{(enbzp)Co}2(μ-L)](ClO4)4·2MeOH (L = bpee, 3; L = bpea, 4). In all of these complexes, each Co(II) center is equatorially chelated by the planar tetradentate ligand enbzp and connected to a chain or dinuclear structure through bpee or bpea ligands along its axial direction. All of the complexes, including their desolvated phases, displayed overall incomplete and gradual SCO properties. Interestingly, the desolvated phase of 1 exhibited an additional non-spin magnetic transition characterized by wide room-temperature hysteresis (>40 K), which was reversible and rate-dependent, showcasing the synergy between SCO and SPT manifested through slow kinetics. We discuss the possible reasons for the distinct features and our findings demonstrate that the combination of a rigid polymeric framework with flexible substituents holds promise for achieving synergy between SCO and SPT.

Concerted flexible and steric strategy in α-diimine nickel and palladium mediated insertion (Co-)Polymerization

To address the issues of poor thermostability of catalyst and low polymer molecular weight resulted from chain transfer at high temperature in olefin polymerization, versatile strategies have been utilized in the benchmark α-diimine nickel and palladium catalysts. In this contribution, a concerted flexible and steric strategy was highlighted in the α-diimine nickel and palladium catalysts. Compared to the seminal Brookhart catalyst, these newly generated nickel catalysts exhibited improved thermostability over a wide range of temperature from 30 °C to 130 °C, showed higher catalytic activities, and produced significantly higher (4.7–5.8 times) molecular weight polymers in ethylene polymerization, which are highly branched polyethylenes (76–110/1000C, SR = 72 %). Notably, high molecular weight polyethylene (up to 219 kg mol−1) was even afforded at 130 °C, which is extremely challenging when the flexible substituent is used in α-diimine system. The corresponding palladium analogues by using the same strategy further produced high molecular weight ethylene-methyl acrylate copolymers (up to 137 kg mol−1) at the difficult 70 °C in the copolymerization of ethylene and methyl acrylate. The incorporation of methyl acrylate could be tuned (0.6–2.9 mol%), where methyl acrylate units distribute both in the main chain and at the end of branches (15 %:85 %).

Probing the Nucleic Acid Flexibility to Disarm the Viral Counter-Defense Machinery: Design and Characterization of Potent p19 Inhibitors.

Plant viruses are highly destructive and significant contributors to several global pandemics and epidemics in plants. A viral disease outbreak in plants can cause a scarcity of food supply and is a severe concern to humanity. The siRNA (small interfering RNA)-mediated RNA-induced silencing complex (RISC) formation is a primary defense mechanism in plants against viruses, where the RISC binds and degrades viral mRNAs. As a counter-defense, many viruses encode RNA-silencing suppressor proteins (e.g., the p19 protein from the Tombusviridae family) for viral proliferation in plants. The functional form of p19 (homodimer) binds to plant siRNA with high affinities, thereby interrupting the RISC formation and thus preventing the viral mRNA silencing in plants. By altering the RISC formation, the p19 protein helps the virus invasion in the plant and ultimately stunts host growth. In this study, we designed several modified siRNA-based molecules for p19 inhibition. The viral p19 protein is known to interact predominantly through H-bonds with 2'-OH and phosphates of the plant siRNA. We utilized this information and in silico-designed flexible substituents of siRNA, where we removed the C2'-C3' bond in each nucleotide unit. We performed all-atom explicit-solvent molecular dynamics simulations (400 ns, 3 replicates each) for control/modified siRNA─p19 complexes (8 in total) followed by energetic estimations. Strikingly, in a few modified complexes, the siRNA not only retained the double-helical structural integrity but also displayed remarkably enhanced p19 binding compared to the control siRNA; hence, we consider it important to perform biological and chemical in vitro and in vivo studies on proposed flexible nucleic acids as p19 inhibitors for crop protection.

Highly Chemoselective Synthesis of Indole Derivatives.

A facile and efficient synthesis of polysubstituted indoles from α-arylamino-β-hydroxy-2-enamides, α-arylamino-β-oxo-amides, or their tautomeric mixture via electrophilic activation strategy is described. The salient feature of this methodology is the use of either combined Hendrickson reagent and triflic anhydride (Tf2O) or triflic acid (TfOH) to control the chemoselectivity in the intramolecular cyclodehydration to provide a predictable approach to these valuable indoles with flexible substituent patterns. Moreover, the mild reaction conditions, simple execution, high chemoselectivity, excellent yields, and wide range of synthetic potential of products make this protocol much attractive for academic research and practical applications.

Insight on the Interaction between the Camptothecin Derivative and DNA Oligomer Mimicking the Target of Topo I Inhibitors.

The understanding of the mechanism of Topo I inhibition by organic ligands is a crucial source of information that has led to the design of more effective and safe pharmaceuticals in oncological chemotherapy. The vast number of inhibitors that have been studied in this respect over the last decades have enabled the creation of a concept of an ‘interfacial inhibitor’, thereby describing the machinery of Topo I inhibition. The central module of action of this machinery is the interface of a Topo I/DNA/inhibitor ternary complex. Most of the ‘interfacial inhibitors’ are primarily kinetic inhibitors that form molecular complexes with an “on–off” rate timing; therefore, all of the contacts between the inhibitor and both the enzyme and the DNA are essential to keep the complex stable and reduce the “off rate”. To test this hypothesis, we designed the compound using a C-9-(N-(2′-hydroxyethyl)amino)methyl substituent in an SN38 core, with a view that a flexible substituent may bind inside the nick of a model of the DNA and stabilize the complex, leading to a reduction in the “off rate” of a ligand in a potential ternary complex in vivo. Using docking analysis and molecular dynamics, free energy calculations on the level of the MM-PBSA and MM-GBSA model, here we presented the in silico-calculated structure of a ternary complex involving the studied compound 1. This confirmed our suggestion that compound 1 is situated in a groove of the nicked DNA model in a few conformations. The number of hydrogen bonds between the components of a ternary complex was established, which strengthens the complex and supports our view. The docking analysis and free energy calculations for the receptor structures which were obtained in the MD simulations of the ternary complex 1/DNA/Topo I show that the binding constant is stronger than it was for similar complexes with TPT, CPT, and SN38, which are commonly considered as strong Topo I inhibitors. The binary complex structure 1/DNA was calculated and compared with the experimental results of a complex that was in a solution. The analysis of the cross-peaks in NOESY spectra allowed us to assign the dipolar interactions between the given protons in the calculated structures. A DOSY experiment in the solution confirmed the strong binding of a ligand in a binary complex, having a Ka of 746 mM−1, which was compared with a Ka of 3.78 mM−1 for TPT. The MALDI-ToF MS showed the presence of the biohybrid, thus evidencing the occurrence of DNA alkylation by compound 1. Because of it having a strong molecular complex, alkylation is the most efficient way to reduce the “on–off” timing as it acts as a tool that causes the cog to brake in a working gear, and this is this activity we want to highlight in our contribution. Finally, the Topo I inhibition test showed a lower IC50 of the studied compound than it did for CPT and SN38.

Polarity-Dependent Twisted Intramolecular Charge Transfer in Diethylamino Coumarin Revealed by Ultrafast Spectroscopy

Twisting intramolecular charge transfer (TICT) is a common nonradiative relaxation pathway for a molecule with a flexible substituent, effectively reducing the fluorescence quantum yield (FQY) by swift twisting motions. In this work, we investigate coumarin 481 (C481) that contains a diethylamino group in solution by femtosecond transient absorption (fs-TA), femtosecond stimulated Raman spectroscopy (FSRS), and theoretical calculations, aided by coumarin 153 with conformational locking of the alkyl arms as a control sample. In different solvents with decreasing polarity, the transition energy barrier between the fluorescent state and TICT state increases, leading to an increase of the FQY. Correlating the fluorescence decay time constant with solvent polarity and viscosity parameters, the multivariable linear regression analysis indicates that the chromophore’s nonradiative relaxation pathway is affected by both hydrogen (H)-bond donating and accepting capabilities as well as dipolarity of the solvent. Results from the ground- and excited-state FSRS shed important light on structural dynamics of C481 undergoing prompt light-induced intramolecular charge transfer from the diethylamino group toward –C=O and –CF3 groups, while the excited-state C=O stretch marker band tracks initial solvation and vibrational cooling dynamics in aprotic and protic solvents (regardless of polarity) as well as H-bonding dynamics in the fluorescent state for C481 in high-polarity protic solvents like methanol. The uncovered mechanistic insights into the molecular origin for the fluorogenicity of C481 as an environment-polarity sensor substantiate the generality of ultrafast TICT state formation of flexible molecules in solution, and the site-dependent substituent(s) as an effective route to modulate the fluorescence properties for such compact, engineerable, and versatile chemosensors.

Direct Synthesis of Chain-End Toluene Functionalized Hyperbranched Ethylene Oligomers.

Chain-end functionalized polymers play an important role in the field of building complex macromolecular structures. In this study, we have synthesized and characterized four dibenzhydryl iminopyridine Ni(II) complexes bearing remote flexible substituents (Et and n-Bu) to provide hyperbranched ethylene oligomers in ethylene oligomerization with moderate to good activities. Most notably, toluene-end-functionalized hyperbranched ethylene oligomers were obtained under elevated temperature conditions and validated by NMR. The tandem catalysis of ethylene oligomerization and the subsequent Friedel–Crafts addition of the resulting unsaturated products to toluene molecules was proposed as the cause of the observed phenomenon.

Dynamic Docking of Macrocycles in Bound and Unbound Protein Structures with DynaDock.

Macrocycles are interesting molecules with unique features due to their conformationally constrained yet flexible ring structure. This characteristic poses a difficult challenge for computational modeling studies since they rely on accurate structural descriptions. In particular, molecular docking calculations suffer from the lack of ring flexibility during pose generation, which is often compensated by using pregenerated ligand conformer ensembles. Moreover, receptor structures are mainly treated rigidly, which limits the use of many docking tools. In this study, we optimized our previous molecular dynamics-based sampling and docking pipeline specifically designed for the accurate prediction of macrocyclic compounds. We developed a dihedral classification procedure for in-depth conformational analysis of the macrocyclic rings and extracted structural ensembles that were subsequently docked in both bound and unbound protein structures employing a fully flexible approach. Our results suggest that including a ring conformer close to the bound state in the starting ensemble increases the chance of successful docking. The bioactive conformations of a diverse set of ligands could be predicted with high and decent accuracy in bound and unbound protein structures, respectively, due to the incorporation of full molecular flexibility in our approach. The remaining unsuccessful docking calculations were mainly caused by large flexible substituents that bind to surface-exposed binding sites, rather than the macrocyclic ring per se and could be further improved by explicit molecular dynamics simulations of the docked complex.

NHC–BIAN–Cu(I)-Catalyzed Friedländer-Type Annulation of 2-Amino-3-(per)fluoroacetylpyridines with Alkynes on Water

The direct catalytic alkynylation/dehydrative cyclization of 2-amino-3-trifluoroacetyl-pyridines on water was developed for the efficient synthesis of a broad range of fluorinated 1,8-naphthyridines from terminal alkynes. A novel N-heterocyclic carbene (NHC) ligand system that combines a π-extended acenaphthylene backbone with sterically bulky pentiptycene pendant groups was successfully utilized in a copper- or silver-mediated cyclization. Computational analysis of the reaction pathway supports our explanation of the different experimental conversions and yields for the set of copper and silver catalysts. The impact of steric hindrance at the metal center and the flexibility of substituents on the imidazole ring of the NHC on catalytic performance are also discussed.

Regulation of the Assembled Structure of a Flexible Porphyrin Derivative Containing Tetra Isophthalic Acids by Coronene or Different Pyridines.

Based on previous research, a new coassembly formed by a porphyrin derivative (IPETPP), which contains a flexible substituent of m-phthalic acid, is observed with coronene (COR) molecules at a higher concentration. Besides, a fresh IPETPP self-assembly formed at a lower concentration and another new coassembly with COR molecules are obtained. Moreover, the addition of a series of bipyridines alters the diamond arrangement of IPETPP, which enhances the stability of the two-component structures. It is unprecedented that bipyridine derivatives break intermolecular hydrogen bonds containing m-phthalic acid substituents. All the coassemblies are investigated by scanning tunneling microscopy on a highly oriented pyrolytic graphite. Combined with density functional theory, the formation mechanism of the assembled structures is revealed. These results would contribute to understanding the interfacial crystal behaviors and probably provide an efficient pathway to regulate the binary structures.

Modifying polynitro benzene and pyrazine skeletons with flexible nitratoethyl substituents towards new energetic melt-castable materials

The development of new energetic melt-castable materials that can replace trinitrotoluene (TNT) is an important focus in energetic material research. Here, we developed a promising strategy for incorporating energetic flexible substituent groups onto a high-melting-point molecular skeleton to develop new energetic melt-castable materials. Using this method, five nitratoethyl-functionalized polynitro benzenes and pyrazines were synthesized. Among the prepared compounds, 1-(2-nitrato-ethylamino)-2,4,6-trinitrobenzene (MSR-1) and 1-bis(2-nitrato-ethyl)amine-2,4,6-trinitrobenzene (MSR-2) exhibited the potential as energetic melt-castable materials due to the desirable wide temperature range over which the materials were liquid, ranging from the melting point (Tm: 90.5 °C and 104.8 °C, respectively) to the high decomposition temperatures (Td: 204.7 °C and 208.8 °C, respectively). Moreover, their densities (1.68 g cm−3, 1.71 g cm−3, respectively), detonation performances (7654 m s−1, 7802 m s−1, respectively) and impact sensitivities (20 J) were superior to those of TNT (1.65 g cm−3, 7303 m s−1, 15 J, respectively). A quantitative and accurate method of binding energy in cluster (BEC) is proposed to account for the melting-point differences in the prepared energetic compounds. The average binding energy between the close-contacting dimers in the molecular clusters showed strongly positive correlation with the molecular melting point.

Impact of substituents on the performance of small-molecule semiconductors in organic photovoltaic devices via regulating morphology

This review summarizes recent prominent examples of substituent engineering on small-molecule organic semiconductors for photovoltaic applications, focusing on flexible substituents that regulate the active-layer morphology.

Study on thermodynamic property of pyrrolylaldiminate dialkyl-aluminum (Methyl- and Ethyl- substituted) complexes

Pyrrolylaldiminate dialkyl-aluminum (methyl- and ethyl- substituted) complexes with different substituents were prepared and characterized. Single-crystal X-ray diffraction proved that compound 2A [(PyrImEt)AlMe2] is a monomer with a planar five-membered ring structure. The optimized structure of density functional theory (DFT) shows that compound 5A [(PyrImcPr)AlMe2] and compound 6A [(PyrImiPr)AlMe2] is a monomer and planar five-membered ring structure. Pyrrolylaldiminate dialkyl-aluminum complexes have fluorescence properties and accord with the characteristics of rigid planar complexes. Based on the monomer and the planar structure of pyrrolylaldiminate dialkyl-aluminum complexes, we further studied the complex's thermodynamic properties from the aspects of thermogravimetric (TGA), Differential Scanning Calorimeter (DSC), and InP-T−1 (Vapor pressure-temperature functions). The results of TGA and DSC showed that the pyrrolylaldiminate dialkyl-aluminum complex with planar structure has good thermal stability. When controlling the chain length of substituents, dimethyl-aluminum complexes with low melting points can be prepared. Substituents’ effect on the complex's volatilization was investigated according to the vapor pressure-temperature function. Overall, Tvapor pressure atP=1Torr of complexes with small molecular weight is low (Tvapor pressure atP=1Torr of pyrrolylaldiminate dimethyl-aluminum complexes is 60–85 °C, and Tvapor pressure atP=1Torr of pyrrolylaldiminate diethyl‑aluminum complexes is 75–103 °C). Pyrrolylaldiminate dialkyl-aluminum complexes have good thermal stability and volatility, consistent with the requirements of atomic layer deposition. The effect of substituents on the enthalpy of evaporation (ΔHvapour) of dimethyl-aluminum [56.83–89.80 kJ.mol−1] and diethyl‑aluminum complexes [76.52–83.58 kJ.mol−1] is different, and ΔHvapour of dimethyl-aluminum complexes is more easily affected by substituents. For diethyl‑aluminum complexes, the flexible substituent has little effect on ΔHvapour of the complexes.

Total Synthesis of Geldanamycin.

The total synthesis of geldanamycin, a well-known polyketide that exhibited potent anticancer activity by inhibiting Hsp90, was finished in 26 long linear steps with 2.65% overall yield. High convergency of the synthesis was achieved by the disconnection between C12 and C13 that gives C5-C12 and C13-C21 fragments as major building blocks. The use of an alkynyl ketone as the precursor of the C5-C12 fragment enabled a reagent-controlled establishment of C7 chirality and a highly flexible substituent exchange at C8, making the synthetic route suitable for deep-seated structural modifications on geldanamycin.

Pyrazinacenes exhibit on-surface oxidation-state-dependent conformational and self-assembly behaviours

Acenes and azaacenes lie at the core of molecular materials’ applications due to their important optical and electronic features. A critical aspect is provided by their heteroatom multiplicity, which can strongly affect their properties. Here we report pyrazinacenes containing the dihydro-decaazapentacene and dihydro-octaazatetracene chromophores and compare their properties/functions as a model case at an oxidizing metal substrate. We find a distinguished, oxidation-state-dependent conformational adaptation and self-assembly behaviour and discuss the analogies and differences of planar benzo-substituted decaazapentacene and octaazatetracene forms. Our broad experimental and theoretical study reveals that decaazapentacene is stable against oxidation but unstable against reduction, which is in contrast to pentacene, its C–H only analogue. Decaazapentacenes studied here combine a planar molecular backbone with conformationally flexible substituents. They provide a rich model case to understand the properties of a redox-switchable π-electronic system in solution and at interfaces. Pyrazinacenes represent an unusual class of redox-active chromophores.

The synergistic effect of rigid and flexible substituents on insertion polymerization with α-diimine nickel and palladium catalysts

The introduction of flexible cycloalkyl groups greatly enhanced the chain growth in the Ni(ii) catalytic system and facilitated the insertion of polar monomers in the Pd(ii) catalytic system.